A novel sorting method reveals superior metabolic activity of mononucleated over binucleated tetraploid hepatocytes
Watanabe, Y. V.; Sussman, J. H.; Anami, T.; Hattori, M.; Yamane, S.; Nishikawa, M.; Sakai, Y.; Katsuda, T.
Show abstract
Hepatocytes display notable ploidy diversity, varying both in the number of genomic copies and in the number of nuclei. Most mouse hepatocytes are tetraploid (4n), which can exist as either mononucleated (1x4n) or binucleated (2x2n) cells. Despite this distinction, these two cell types have traditionally been grouped and studied as a single population. One likely reason for this is that conventional ploidy-sorting methods classify hepatocytes based solely on total DNA content, without distinguishing between mononucleated and binucleated states. In this study, we developed a novel flow cytometry strategy to distinguish and isolate 1x4n and 2x2n hepatocytes. Our approach leverages Hoechst-Area to assess total ploidy and Hoechst-Height to differentiate mononucleated and binucleated hepatocytes. Transcriptome analysis comparing these two populations revealed that 1x4n hepatocytes exhibit a broader and more metabolically active gene expression profile. Importantly, this enhanced metabolic activity was independent of liver zonation, a well-known driver of metabolic heterogeneity in hepatocytes. Our findings uncover a previously underappreciated layer of functional diversity in the liver and provide a new framework for studying the physiological and pathological roles of nuclear configuration in hepatocytes.
Matching journals
The top 13 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure 95%
- The Essential Role of O-GlcNAcylation in Hepatic Differentiation 94%
- Hepatic MCPIP1 protein levels are reduced in NAFLD patients and are predominantly expressed in cholangiocytes and liver endothelium 93%
Similar papers in this journal
- Differential modulation of miR-122 transcription by TGFbeta1/BMP6: implications for nonresolving inflammation and hepatocarcinogenesis 93%
- Therapeutic potential of SOX9 dysruption in Combined Hepatocellular Carcinoma-Cholangiocarcinoma 92%
- Oncofetal protein CRIPTO regulates wound healing and fibrogenesis in regenerating liver and is associated with the initial stages of cardiac fibrosis 92%
Similar papers in this journal
- Characterization of regulatory transcriptional mechanisms in hepatocyte lipotoxicity 93%
- Reproducible and sensitive micro-tissue RNA-sequencing from formalin-fixed paraffin-embedded tissue for spatial gene expression analysis 93%
- Diet-induced rewiring of the Wnt gene regulatory network connects aberrant splicing to fatty liver and liver cancer in DIAMOND mice 92%
Similar papers in this journal
- Vagus nerve mediated liver-brain axis is a major regulator of the metabolic landscape in the liver 92%
- An optimized workflow for analyzing extracellular vesicles as biomarkers in liver diseases. 92%
- Disrupted Post-Transcriptional Regulation of Gene Expression as A Hallmark of Fatty Liver Progression 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.